Oral AML regimen cuts burden, keeps outcomes

Clinical takeaway: The oral regimen is a reasonable alternative to intravenous standard care when intensive chemo is not an option, sparing monthly clinic visits but requiring early bone marrow assessment and venetoclax pauses to manage cytopenias.

Older and unfit patients with acute myeloid leukemia (AML) already have an effective standard: venetoclax plus a hypomethylating agent such as decitabine. But the hypomethylating agent is given intravenously over five to seven days every cycle, indefinitely, which means repeated clinic or hospital visits for people least able to tolerate them. The ASCERTAIN-V trial tested whether swapping in an oral form of decitabine, paired with cedazuridine to keep it from breaking down when swallowed, could match that standard without the infusions.

In the pivotal phase 2b cohort, 47% of patients achieved a complete response, and 63% reached either a complete response or complete response with incomplete hematologic recovery. Among complete responders, 75% still had an ongoing response at 12 months. Median overall survival was 15.5 months, in line with what intravenous regimens deliver in this population. The result cleared the trial's prespecified efficacy bar, which required the lower bound of the confidence interval to beat the 17.9% complete-response rate historically seen with hypomethylating agents alone.

The trial's second contribution was learning how to dose the regimen. Early cohorts saw substantial myelosuppression, so investigators began checking bone marrow as early as cycle 1 on day 21 and pausing venetoclax once blasts cleared, letting counts recover before the next cycle. Days of venetoclax dropped with each cycle, and serious adverse events fell with them: febrile neutropenia, the most common serious event, occurred in 39% of responders during cycles 1 or 2 but only 14% by cycles 3 or 4. Median overall survival appeared to improve across the trial phases as these adjustments took hold.

This was an open-label, nonrandomized phase 1-2 trial of 189 newly diagnosed patients across 34 centers in the US, Canada, and Spain, all either 75 or older or unfit for intensive chemo. The safety profile held no surprises: grade 3 or higher anemia, neutropenia, and febrile neutropenia were the common events, consistent with what the drug class already produces. Mortality was 3% at 30 days and 10% at 60 days.

The practical bottleneck is not efficacy but management. The regimen works, but it depends on clinicians doing the early marrow checks and schedule pauses that the trial worked out; without them, the myelosuppression that dragged the earliest cohort returns. The combination won FDA approval on May 13 for newly diagnosed adults 75 or older or unable to undergo intensive chemo. The trial was not randomized against intravenous standard care and did not measure quality of life or health care use directly, so the burden advantage rests on the shift in route rather than on head-to-head data.

"The goal of the all-oral therapy is to keep people out of the hospital, especially once they have achieved remission," said lead author Gail Roboz, MD, director of the Clinical and Translational Leukemia Program at Weill Cornell Medicine. "Patients are thrilled not to have to deal with monthly chemotherapy injections or infusions."

Source: Roboz GJ. N Engl J Med. 2026 Jun 4. All-oral treatment of newly diagnosed acute myeloid leukemia